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PubMed2003

Evolutionary indicators of human immunodeficiency virus type 1 reservoirs and compartments.

In vivo virologic compartments are cell types or tissues between which there is a restriction of virus flow, while virologic reservoirs are cell types or tissues in which there is a relative restriction of replication. The distinction between reservoirs and compartments is important because therapies that would be effective against a reservoir may not be effective against viruses produced by a given compartment, and vice versa. For example, the use of cytokines to "flush out" long-lived infected cells in patients on highly active antiretroviral therapy (T. W. Chun, D. Engel, M. M. Berrey, T. Shea, L. Corey, and A. S. Fauci, Proc. Natl. Acad. Sci. USA 95:8869-8873, 1998) may be successful for a latent reservoir but may not impact a compartment in which virus continues to replicate because of poor drug penetration. Here, we suggest phylogenetic criteria to illustrate, define, and differentiate between reservoirs and compartments. We then apply these criteria to the analysis of simulated and actual human immunodeficiency virus type 1 sequence data sets. We report that existing statistical methods work quite well at detecting viral compartments, and we learn from simulations that viral divergence from a calculated most recent common ancestor is a strong predictor of viral reservoirs.

Algorithms↗

PubMed2005

[Acute infectious (not Clostridium difficile-associated) diarrhea in the elderly].

Acute diarrhoea, non-antibiotic associated, is a common problem and a significant cause of morbidity and mortality in old age. In most cases diarrhoea has an infectious etiology. A number of different micro organisms can cause infectious diarrhoea. Most frequent are viral infections with a benign evolution. Rehydration is the only important therapeutic measure. Infections with bacteria are less common, antibiotics should be prescribed only in severe cases, and when there is suspicion of invasive infections by enteropathogenic bacteria.

Acute Disease↗

PubMed1989

[Experimental herpes simplex keratitis in rabbits. Evaluation of pro-infectious effects of topical non-steroidal anti-inflammatory agents].

We tested 3 non steroidal anti-inflammatory drugs in experimental herpes keratitis in order to determine possible pro-infectious consequences. The drugs were Indomethacine, Flurbiprofen and a new non steroidal anti-inflammatory, CBS 113 A, mixed inhibitor of cycloxygenase and lipoxygenase. We studied simultaneously the evolution of the keratitis and viral excretion. We considered that an anti-inflammatory agent had a pro-infectious effect if the keratitis was more serious and/or viral excretion longer in comparison with placebo. We have shown, for the 3 drugs, in comparison with dexamethasone activity, absence of a pro-infectious effect. We compared our results on Flurpiprofen with an other study which gave this anti-inflammatory drug pro-infectious capacities; the concentration used was higher. CBS 113 A, inhibiting the metabolism of arachidonic acid via lipoxygenase and cycloxygenase and thus preventing the formation of metabolitis involved in inflammation (prostaglandins, leukotrienes,...), should have a spectrum of activity wider than that of NSAID. Subject to further studies, these 3 nonsteroidal anti-inflammatory could be used in herpetic kerato-uveitis.

Administration, Topical↗

PubMed2004

HIV evolution: CTL escape mutation and reversion after transmission.

Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

Adult↗

PubMed2003

Exchange of genetic sequences of long terminal repeat and the env gene by a promiscuous primate type D retrovirus.

Squirrel monkey retrovirus (SMRV) is a New World primate type D retrovirus. It was shown that SMRV-related sequences could be detected in another New World species, the skunk. It was further suggested that SMRV and an Old World primate type C retrovirus, baboon endogenous virus (BaEV), may have exchanged their env gene sequences. In this study, we sought to understand which sequences were exchanged between the genomic DNAs of SMRV and skunk. We also sought to determine the sequences exchanged between SMRV and BaEV. Here, we demonstrate that the long terminal repeat of SMRV is present in the skunk genome. We also show, by nucleotide sequence analysis, that the env gene that encodes the p15E glycoprotein of BaEV was most likely transduced from the corresponding gene of a primate type D retrovirus. Our results demonstrate that SMRV is a promiscuous virus with its pol gene homologous to the pol genes of type A, type B and avian type C viruses and a portion of its env gene homologous to the env genes of primate type C retroviruses. However, the primer binding sequence is unique to type D retroviruses. These kinds of recombination are likely to occur more than once in the evolution of retroviruses. The promiscuous nature of retroviruses and the recent incidence of unintended retroviral integration into a gene therapy patient underscore the importance of understanding how retroviral sequences are recombined among themselves and how they are integrated into the mammalian genome.

Amino Acid Sequence↗

PubMed2002

Evolution of DNA polymerase families: evidences for multiple gene exchange between cellular and viral proteins.

A phylogenetic analysis of the five major families of DNA polymerase is presented. Viral and plasmid sequences are included in this compilation along with cellular enzymes. The classification by Ito and Braithwaite (Ito and Braithwaite 1991) of the A, B, C, D, and X families has been extended to accommodate the "Y family" of DNA polymerases that are related to the eukaryotic RAD30 and the bacterial UmuC gene products. After analysis, our data suggest that no DNA polymerase family was universally conserved among the three biological domains and no simple evolutionary scenario could explain that observation. Furthermore, viruses and plasmids carry a remarkably diverse set of DNA polymerase genes, suggesting that lateral gene transfer is frequent and includes non-orthologous gene displacements between cells and viruses. The relationships between viral and host genes appear very complex. We propose that the gamma DNA polymerase of the mitochondrion replication apparatus is of phage origin and that this gene replaced the one in the bacterial ancestor. Often there was no obvious relation between the viral and the host DNA polymerase, but an interesting exception concerned the family B enzymes: in which ancient gene exchange can be detected between the viruses and their hosts. Additional evidence for horizontal gene transfers between cells and viruses comes from an analysis of the small damage-inducible DNA polymerases. Taken together, these findings suggest a complex evolutionary history of the DNA replication apparatus that involved significant exchanges between viruses, plasmids, and their hosts.

Animals↗

PubMed1987

Molecular evolutionary rates of oncogenes.

Using nine sets of viral and cellular oncogenes, the rates of nucleotide substitutions were computed by using Gojobori and Yokoyama's (1985) method. The results obtained confirmed our previous conclusion that the rates of nucleotide substitution for the viral oncogenes are about a million times higher than those for their cellular counterparts. For cellular oncogenes and most viral oncogenes, however, the rate of synonymous substitution is higher than that of nonsynonymous substitution. Moreover, the pattern of nucleotide substitutions for viral oncogenes is more similar to that for functional genes (such as cellular oncogenes) than for pseudogenes. This implies that nucleotide substitutions in viral oncogenes may be functionally constrained. Thus, our observation supports that nucleotide substitutions for the oncogenes in those DNA and RNA genomes are consistent with Kimura's neutral theory of molecular evolution (Kimura 1968, 1983).

Animals↗

PubMed2006

Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus in Uganda and K1 gene evolution within the host.

BACKGROUND: Epidemiological studies of Kaposi sarcoma (KS)-related herpesvirus (KSHV) indicate that having a KSHV-seropositive mother is a risk factor for KSHV infection in children. METHODS: We determined the KSHV K1 sequences in concordantly polymerase chain reaction-positive Ugandan mother-child pairs, to ascertain whether they shared the same viral strain. We also examined sequences amplified from saliva and buffy coat samples from the same subjects, to investigate potential intrasubject sequence differences. RESULTS: We obtained K1 sequences from 6 of 10 mother-child pairs. In 1 pair, the subtypes differed between mother and child. The mother and child in 2 other pairs shared the same subtype, but the sequences differed. The mother and child in 2 pairs shared KSHV strains with exact (100%) nucleotide homology. The last pair showed evidence of viral strain concordance between mother and child but also showed evidence of evolution of the viral sequence within the child. Of 26 study subjects, 19 showed no evidence of intrasubject K1 sequence variability, but, in 7 subjects, all of whom were children, amino acid variation of 1%-4% was observed. CONCLUSIONS: Our findings are consistent with KSHV transmission from maternal and nonmaternal sources in KS-endemic regions. Our results also provide evidence for ongoing evolution of the K1 gene in KSHV-infected children.

Amino Acid Sequence↗

PubMedDate not supplied

Genetic reassortment and patch repair by recombination in retroviruses.

Retroviral particles contain a diploid RNA genome which serves as template for the synthesis of double-stranded DNA in a complex process guided by virus-encoded reverse transcriptase. The dimeric nature of the genome allows the proceeding polymerase to switch templates during copying of the copackaged RNA molecules, leading to the generation of recombinant proviruses that harbor genetic information derived from both parental RNAs. Template switching abilities of reverse transcriptase facilitate the development of mosaic retroviruses with altered functional properties and thereby contribute to the restoration and evolution of retroviruses facing altering selective forces of their environment. This review focuses on the genetic patchwork of retroviruses and how mixing of sequence patches by recombination may lead to repair in terms of re-established replication and facilitate increased viral fitness, enhanced pathogenic potential, and altered virus tropisms. Endogenous retroelements represent an affluent source of functional viral sequences which may hitchhike with virions and serve as sequence donors in patch repair. We describe here the involvement of endogenous viruses in genetic reassortment and patch repair and review important examples derived from cell culture and animal studies. Moreover, we discuss how the patch repair phenomenon may challenge both safe usage of retrovirus-based gene vehicles in human gene therapy and the use of animal organs as xenografts in humans. Finally, the ongoing mixing of distinct human immunodeficiency virus strains and its implications for antiviral treatment is discussed.

Animals↗

PubMed2000

In vitro selection of novel RNA ligands that bind human cytomegalovirus and block viral infection.

Ribonuclease-resistant RNA molecules that bind to infectious human cytomegalovirus (HCMV) were isolated in vitro from a pool of randomized sequences after 16 cycles of selection and amplification. The two ligands (L13 and L19) characterized exhibited high HCMV-binding affinity in vitro and effectively inhibited viral infection in tissue culture. Their antiviral activity was also specific as they only reacted with two different strains of HCMV but not with the related herpes simplex virus 1 and human cells. These two ligands appeared to function as antivirals by blocking viral entry. Ultraviolet (UV) crosslinking studies suggested that L13 and L19 bind to HCMV essential glycoproteins B and H, respectively. Thus, RNA ligands that bind to different surface antigens of HCMV can be simultaneously isolated by the selection procedure. Our study demonstrates the feasibility of using these RNA ligands as a research tool to identify viral proteins required for infectivity and as an antiviral agent to block viral infection.

Antiviral Agents↗

PubMed1997

Genital papillomaviruses (PVs) and epidermodysplasia verruciformis PVs occur in the same monkey species: implications for PV evolution.

Portions of the genome from two different papillomaviruses (PVs) of the Abyssinian Colobus monkey were sequenced and phylogenetically analyzed. This revealed that the major evolutionary separation between genital PVs and epidermodysplasia verruciformis-associated PVs (EV-PVs) hitherto found only in human papillomaviruses (HPVs) also exists in animal PVs. The sequence of the long control region (LCR) of Colobus monkey PV type 2 (CgPV-2) reveals a small size and an arrangement of potential cis-responsive elements typical of the EV-HPVs; namely four binding sites for the viral E2 protein, with one of them being located within the L1 gene, a cluster of nuclear factor I (NFI)- and AP-1-binding sites and a 50-bp sequence upstream of the E6 gene consisting only of the nucleotides A and T. This level of conservation of functional elements within the highly variable LCR suggests that CgPV-2 could be adopted as a model for studying human skin cancer associated with EV-HPVs. Although isolated from the same monkey species, the other Colobus monkey PV, CgPV-1, is a typical genital PV as shown by E1 and L1 sequence comparisons. The presence of these two major phylogenetic divisions of PVs in both human and monkey hosts strongly suggests that this diversification predated the evolutionary split between monkeys and apes. In other words, at least two different groups of PVs have been evolving separately in their respective primate hosts for more than 22 million years with only moderate sequence changes since their genesis.

Animals↗

PubMedDate not supplied

[Information value of various trinucleotides of some genetic systems].

New method to reveal the sites in genomes obtaining the high information capacity is developed. A distribution of those sites of the length 3 among 16 viral genomes and 11 bacteriophages genomes has been studied. It is shown that some triplets with high information capacity occur in a family of relatively close genomes with the increased frequency. The molecular evolution aspects of a persistence of highly scored sites with respect to their information capacity among various genomes are discussed.

Adenoviridae↗

PubMed1983

Antigenicity and evolution amongst recent influenza viruses of H1N1 subtype.

The sequence of the HA1 subunit region of the haemagglutinin gene of influenza A/USSR/90/77, and A/Brazil/11/78, A/Lackland/3/78, A/England/333/80 and A/India/6263/80 was determined by dideoxy-sequencing methods using total virion RNA and specific oligonucleotide primers for reverse transcriptase. These 1977-1980 strains share a minimum of 85% amino acid sequence homology with influenza A/PR/8/34. Most of the surface amino acid substitutions which occurred during the evolution of A/PR/8/34 to A/USSR/90/77 and subsequently in the 1978-1980 strains are located in the 4 antigenic sites previously defined by an analysis of laboratory-selected mutants of A/PR/8/34. We deduce an evolutionary pathway for the 1977-80 strains and suggest their different epidemic properties may be a consequence of only a few amino acid changes.

Antigens, Viral↗

PubMed1985

Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene.

The entire nucleotide sequence of an infectious clone of human T-cell leukemia virus type II provirus was determined. This provirus consists of 8952 nucleotides. In addition to long terminal repeats and gag, pol, env, and X, a protease gene that is responsible for processing the gag precursor protein was found. The protease gene is encoded in a different frame from gag and pol and was located between the gag and pol open reading frames. The 5' region of the protease gene overlaps the 3' gag region. Coding regions of the provirus show about 60% homology with those of human T-cell leukemia virus type I at the nucleotide level. The evolutionary relationship between human T-cell leukemia virus types I and II is discussed.

Antigens, Viral↗

PubMed1992

Rapid sequence evolution of street rabies glycoprotein is related to the highly heterogeneous nature of the viral population.

The sequence of the glycoprotein gene of a street rabies virus was determined directly using fragments of a rabid dog brain after PCR amplification. Compared with that of the prototype strain CVS, this sequence displayed 10% divergence in overall amino acid composition. However only 6% divergence was noted in the ectodomain suggesting that structural constraints are exerted on this portion of the glycoprotein. A human strain isolated on cell culture from the saliva of a patient with clinical rabies had only five amino acid differences with the canine isolate, an indication of their close relatedness. These differences could have originated during transmission from dog to dog, or from dog to man, or during isolation on cell culture; they are nonetheless indicative of a genetic evolution of street rabies virus. This evolution was further evidenced by the selection of cell-adapted variants which displayed new amino acid substitutions in the glycoprotein. One of them concerned antigenic site III where arginine at position 333 was replaced by glutamine. As expected this substitution conferred resistance to a site IIIa monoclonal antibody (MAb), but surprisingly did not abolish neurovirulence for adult mice. However, a decrease in the neurovirulence of the cell-adapted variant in the presence of a site IIIa specific MAb was noted, suggesting that neurovirulence was due to a subpopulation neutralizable by the MAb. Simultaneous presence of both the parental and variant sequences was indeed evidenced in the brain of a mouse inoculated with the cell-adapted variant; during multiplication in the mouse brain, the frequency of the parental sequence rose from less than 10% to nearly 50%, indicating the selective advantage conferred by arginine 333 in nervous tissue. Altogether these results were suggestive of an intrinsic heterogeneity of street rabies virus. This heterogeneity was further demonstrated by the sequencing of molecular clones of the glycoprotein gene, which revealed that only one-third of the viral genomes present in the brain of a rabid dog had the consensus sequence. Two-thirds of the clones analyzed displayed from one to three amino acid substitutions. Such heterogeneous populations have been referred to as quasispecies, a concept which implies heterogeneous populations kept together in a dynamic equilibrium. This equilibrium could be rapidly displaced, giving the virus the capacity to adapt easily to new environmental conditions.

Amino Acid Sequence↗

PubMed2025

Making sense of the virome in light of evolution and ecology.

Understanding the patterns and drivers of viral prevalence and abundance is of key importance for understanding pathogen emergence. Over the last decade, metagenomic sequencing has exponentially expanded our knowledge of the diversity and evolution of viruses associated with all domains of life. However, as most of these 'virome' studies are primarily descriptive, our understanding of the predictors of virus prevalence, abundance and diversity, and their variation in space and time, remains limited. For example, we do not yet understand the relative importance of ecological predictors (e.g. seasonality and habitat) versus evolutionary predictors (e.g. host and virus phylogenies) in driving virus prevalence and diversity. Few studies are set up to reveal the factors that predict the virome composition of individual hosts, populations or species. In addition, most studies of virus ecology represent a snapshot of single species viromes at a single point in time and space. Fortunately, recent studies have begun to use metagenomic data to directly test hypotheses about the evolutionary and ecological factors which drive virus prevalence, sharing and diversity. By synthesizing evidence across studies, we present some over-arching ecological and evolutionary patterns in virome composition, and illustrate the need for additional work to quantify the drivers of virus prevalence and diversity.

Virome↗

PubMed2002

[Verrucous carcinoma and Buschke-Lowenstein tumors: apropos of 2 cases].

The authors present two cases of verrucous carcinomas on Buschke-Lowenstein tumor. The Buschke-Lowenstein tumor is an epithelial sexually transmissible benign tumor of viral origin. Under the influence of oncogenic papillomavirus types 16 and 18 it can become malignant tumor which relations with the verrucous carcinoma, tumor with low grade and essentially local malignancy are still discussed. This evolution follows the alteration by a viral protein of the functions of the tumor suppressor protein P 53. The surgery remains the reference treatment although there is a possibility of frequent recurrences. Radiation therapy and chemotherapy were suggested as adjuvant treatments for the complicated sorts.

Adult↗

PubMed2002

Origins of human virus diversity.

The diverse consequences of different viral infections on the human population reflect both the history of their origins and the nature of their ongoing evolution. Advances in the ease of finding and characterizing viral genome sequences are having a major impact on our understanding of the diversity of human viruses and of their relatives infecting other species.

Evolution, Molecular↗